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1.
PLoS Pathog ; 16(2): e1008102, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32027727

RESUMEN

Understanding the circumstances under which arboviruses emerge is critical for the development of targeted control and prevention strategies. This is highlighted by the emergence of chikungunya and Zika viruses in the New World. However, to comprehensively understand the ways in which viruses emerge and persist, factors influencing reductions in virus activity must also be understood. Western equine encephalitis virus (WEEV), which declined during the late 20th century in apparent enzootic circulation as well as equine and human disease incidence, provides a unique case study on how reductions in virus activity can be understood by studying evolutionary trends and mechanisms. Previously, we showed using phylogenetics that during this period of decline, six amino acid residues appeared to be positively selected. To assess more directly the effect of these mutations, we utilized reverse genetics and competition fitness assays in the enzootic host and vector (house sparrows and Culex tarsalis mosquitoes). We observed that the mutations contemporary with reductions in WEEV circulation and disease that were non-conserved with respect to amino acid properties had a positive effect on enzootic fitness. We also assessed the effects of these mutations on virulence in the Syrian-Golden hamster model in relation to a general trend of increased virulence in older isolates. However, no change effect on virulence was observed based on these mutations. Thus, while WEEV apparently underwent positive selection for infection of enzootic hosts, residues associated with mammalian virulence were likely eliminated from the population by genetic drift or negative selection. These findings suggest that ecologic factors rather than fitness for natural transmission likely caused decreased levels of enzootic WEEV circulation during the late 20th century.

2.
Artículo en Inglés | MEDLINE | ID: mdl-32011597

RESUMEN

INTRODUCTION: In 2016, Puerto Rico became the focal point of the Zika epidemic, with more than 36 000 laboratory-confirmed cases before August. The Puerto Rico Department of Health (PRDH) responded by providing tests to symptomatic and asymptomatic pregnant women. The increased demand for Zika testing placed unprecedented strain on the laboratory capacity and information management processes used within the PRDH. The PRDH recognized the need to have an updated informatics system that securely manages, stores, and transmits digital data. The Centers for Disease Control and Prevention funded the Public Health Informatics Institute to collaborate with the PRDH to assess and improve the informatics capability to respond to the ongoing Zika virus transmission in Puerto Rico. APPROACH: The team employed a 4-component approach to assess the informatics system and improve the information management processes for laboratory testing and reporting of arboviral diseases (Zika, chikungunya, and dengue). The method consisted of a (1) needs assessment, (2) business process analysis and requirements definition, (3) vendor analysis, and (4) solution implementation. RESULTS: The needs assessment determined that the PRDH's procedures for arbovirus testing and reporting were highly complex and paper-based and thus did not maximize the use of existing technology. The solution was to build a Web portal. The business process analysis yielded information to create a map of the flow of specimens, an arbovirus context diagram, and more than 200 requirements. The requirements identified in this process guided the design and creation of the Web portal. DISCUSSION: This report describes the process to build a Web portal to enhance laboratory testing and electronic reporting of Zika cases during the 2016 epidemic in Puerto Rico. We demonstrate the utility of applying the Collaborative Requirements Development Methodology, a proven informatics method, to the development of a Web portal for managing arboviruses in a health department.

3.
J Womens Health (Larchmt) ; 29(2): 139-147, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32045325

RESUMEN

Scientific evidence demonstrated a causal relationship between Zika virus infection during pregnancy and neurologic abnormalities and other congenital defects. The U.S. government's Zika Virus Disease Contingency Response Plan recognized the importance of preventing unintended pregnancy through access to high-quality family planning services as a primary strategy to reduce adverse Zika-related birth outcomes during the 2016-2017 Zika virus outbreak. The U.S.-affiliated Pacific Islands (USAPI) includes three U.S. territories: American Samoa, the Commonwealth of the Northern Mariana Islands, and Guam, and three independent countries in free association with the United States: the Federated States of Micronesia, the Republic of the Marshall Islands, and the Republic of Palau. Aedes spp. mosquitoes, the primary vector that transmits Zika virus, are common across the Pacific Islands, and in 2016, laboratory-confirmed cases of Zika virus infection in USAPI were reported. CDC conducted a rapid assessment by reviewing available reproductive health data and discussing access to contraception with family planning providers and program staff in all six USAPI jurisdictions between January and May 2017. In this report, we summarize findings from the assessment; discuss strategies developed by jurisdictions to respond to identified needs; and describe a training that was convened to provide technical assistance to USAPI. Similar rapid assessments may be used to identify training and technical assistance needs in other emergency preparedness and response efforts that pose a risk to pregnant women and their infants.

4.
Artículo en Inglés | MEDLINE | ID: mdl-32049261

RESUMEN

Aedes aegypti is associated with epidemic diseases in Brazil, such as urban yellow fever, dengue, and more recently, chikungunya and Zika viruses infections. More information about Ae. aegypti infestation is fundamental to virological surveillance in order to ensure the effectiveness of control measures in use. Thus, the present study aims to identify and compare infestation and infectivity of Ae. aegypti females in Macapa city, Amapa State (Amazon region), Brazil, between the epidemiological weeks 2017/02 and 2018/20. A total number of 303 Ae. aegypti females were collected at 21 fixed collection points, 171 at the 10 collection points in the Marabaixo neighborhood and 132 at the 11 collection points in the Central neighborhood. Among the collected samples, only two were positive for dengue virus, with a 2.08% (2/96 pools) infectivity rate for Marabaixo. The difference between the medians of Ae. aegypti females captured in Central and Marabaixo sites was not statistically significant. The findings indicate similar mosquito infestation levels between the neighborhoods, and a low-level of mosquito infectivity, although dengue virus was found only in Marabaixo. Virological surveillance of Ae. aegypti was important to identify sites of infection and determine possible routes of transmission to enable health surveillance teams to adopt preventive strategies where infected mosquitoes are present and act faster.

5.
J Emerg Manag ; 18(1): 7-14, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32031668

RESUMEN

In our increasingly interconnected world, the potential for emerging infectious diseases (EIDs) to spread globally is of paramount concern. Travel bans-herein defined as the complete restriction of travel from at least one geographic region to at least one other international geographic region-are a potential policy solution to control the global spread of disease. The social, economic, and health-related consequences of travel bans, as well as the available evidence on the effectiveness of travel restrictions in preventing the global spread of influenza, have been previously described. However, the effectiveness of travel bans in reducing the spread of noninfluenza EIDs, characterized by different rates and modes of transmission, is less well understood. This study employs an integrative review approach to summarize the minimal evidence on effectiveness of travel bans to decrease the spread of severe acute respiratory syndrome (SARS), Middle Eastern respiratory syndrome (MERS), Ebola virus disease (EVD), and Zika virus disease (ZVD). We describe and qualify the evidence presented in six modeling studies that assess the effectiveness of travel bans in controlling these noninfluenza EID events. We conclude that there is an urgent need for additional research to inform policy decisions on the use of travel bans and other control measures to control noninfluenza EIDs in advance of the next outbreak.

6.
Expert Opin Drug Discov ; : 1-16, 2020 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-32017639

RESUMEN

Introduction: West Nile virus (WNV) is a neurotropic mosquito-borne flavivirus, which is endemic in many countries, especially in Europe and in North America, where the virus has increased its activity in the recent years. No vaccines nor antiviral drugs are available for the prevention and treatment of WNV infection in humans.Areas covered: This review article describes viral and host targets that have been addressed by anti-WNV drug discovery studies and summarizes the most relevant anti-WNV candidate compounds identified so far, focusing on those showing antiviral efficacy in in vivo models and broad-spectrum anti-flavivirus activity.Expert opinion: The most promising anti-WNV drug candidates target conserved enzymatic motifs in viral NS3 protease and NS5 polymerase and are effective against different flaviviruses. Targeting host factors required for viral infection and replication and modulation of host innate antiviral response are also promising approaches, which may lead to the development of compounds with broad-spectrum antiviral activity, a desirable feature for an antiviral drug.

7.
Epilepsia ; 2020 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-32065676

RESUMEN

OBJECTIVE: To estimate the incidence of epilepsy in children with Zika-related microcephaly in the first 24 months of life; to characterize the associated clinical and electrographic findings; and to summarize the treatment responses. METHODS: We followed a cohort of children, born during the 2015-2016 Zika virus (ZIKV) epidemic in Brazil, with congenital microcephaly and evidence of congenital ZIKV infection on neuroimaging and/or laboratory testing. Neurological assessments were performed at ≤3, 6, 12, 15, 18, 21, and 24 months of life. Serial electroencephalograms were performed over the first 24 months. RESULTS: We evaluated 91 children, of whom 48 were female. In this study sample, the cumulative incidence of epilepsy was 71.4% in the first 24 months, and the main type of seizure was infantile spasms (83.1%). The highest incidence of seizures occurred between 3 and 9 months of age, and the risk remained high until 15 months of age. The incidence of infantile spasms peaked between 4 and 7 months and was followed by an increased incidence of focal epilepsy cases after 12 months of age. Neuroimaging results were available for all children, and 100% were abnormal. Cortical abnormalities were identified in 78.4% of the 74 children evaluated by computed tomography and 100% of the 53 children evaluated by magnetic resonance imaging. Overall, only 46.1% of the 65 children with epilepsy responded to treatment. The most commonly used medication was sodium valproate with or without benzodiazepines, levetiracetam, phenobarbital, and vigabatrin. SIGNIFICANCE: Zika-related microcephaly was associated with high risk of early epilepsy. Seizures typically began after the third month of life, usually as infantile spasms, with atypical electroencephalographic abnormalities. The seizure control rate was low. The onset of seizures in the second year was less frequent and, when it occurred, presented as focal epilepsy.

8.
Front Immunol ; 11: 16, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32038660

RESUMEN

West Nile (WN) virus infection of humans is frequently asymptomatic, but can also lead to WN fever or neuroinvasive disease. CD4 T cells and B cells are critical in the defense against WN virus, and neutralizing antibodies, which are directed against the viral glycoprotein E, are an accepted correlate of protection. For the efficient production of these antibodies, B cells interact directly with CD4 helper T cells that recognize peptides from E or the two other structural proteins (capsid-C and membrane-prM/M) of the virus. However, the specific protein sites yielding such helper epitopes remain unknown. Here, we explored the CD4 T cell response in humans after WN virus infection using a comprehensive library of overlapping peptides covering all three structural proteins. By measuring T cell responses in 29 individuals with either WN virus disease or asymptomatic infection, we showed that CD4 T cells focus on peptides in specific structural elements of C and at the exposed surface of the pre- and postfusion forms of the E protein. Our data indicate that these immunodominant epitopes are recognized in the context of multiple different HLA molecules. Furthermore, we observed that immunodominant antigen regions are structurally conserved and similarly targeted in other mosquito-borne flaviviruses, including dengue, yellow fever, and Zika viruses. Together, these findings indicate a strong impact of virion protein structure on epitope selection and antigenicity, which is an important issue to consider in future vaccine design.

9.
PLoS Negl Trop Dis ; 14(2): e0008034, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32017766

RESUMEN

BACKGROUND: Zika virus has recently spread to South- and Central America, causing congenital birth defects and neurological complications. Many people at risk are flavivirus pre-immune due to prior infections with other flaviviruses (e.g. dengue virus) or flavivirus vaccinations. Since pre-existing cross-reactive immunity can potentially modulate antibody responses to Zika virus infection and may affect the outcome of disease, we analyzed fine-specificity as well as virus-neutralizing and infection-enhancing activities of antibodies induced by a primary Zika virus infection in flavivirus-naïve as well as yellow fever- and/or tick-borne encephalitis-vaccinated individuals. METHODOLOGY: Antibodies in sera from convalescent Zika patients with and without vaccine-induced immunity were assessed by ELISA with respect to Zika virus-specificity and flavivirus cross-reactivity. Functional analyses included virus neutralization and infection-enhancement. The contribution of IgM and cross-reactive antibodies to these properties was determined by depletion experiments. PRINCIPAL FINDINGS: Pre-existing flavivirus immunity had a strong influence on the antibody response in primary Zika virus infections, resulting in higher titers of broadly flavivirus cross-reactive antibodies and slightly lower levels of Zika virus-specific IgM. Antibody-dependent enhancement (ADE) of Zika virus was mediated by sub-neutralizing concentrations of specific IgG but not by cross-reactive antibodies. This effect was potently counteracted by the presence of neutralizing IgM. Broadly cross-reactive antibodies were able to both neutralize and enhance infection of dengue virus but not Zika virus, indicating a different exposure of conserved sequence elements in the two viruses. CONCLUSIONS: Our data point to an important role of flavivirus-specific IgM during the transient early stages of infection, by contributing substantially to neutralization and by counteracting ADE. In addition, our results highlight structural differences between strains of Zika and dengue viruses that are used for analyzing infection-enhancement by cross-reactive antibodies. These findings underscore the possible impact of specific antibody patterns on flavivirus disease and vaccination efficacy.

10.
Nat Med ; 26(2): 228-235, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32015557

RESUMEN

Zika virus (ZIKV) has caused significant disease, with widespread cases of neurological pathology and congenital neurologic defects. Rapid vaccine development has led to a number of candidates capable of eliciting potent ZIKV-neutralizing antibodies (reviewed in refs. 1-3). Despite advances in vaccine development, it remains unclear how ZIKV vaccination affects immune responses in humans with prior flavivirus immunity. Here we show that a single-dose immunization of ZIKV purified inactivated vaccine (ZPIV)4-7 in a dengue virus (DENV)-experienced human elicited potent cross-neutralizing antibodies to both ZIKV and DENV. Using a unique ZIKV virion-based sorting strategy, we isolated and characterized multiple antibodies, including one termed MZ4, which targets a novel site of vulnerability centered on the Envelope (E) domain I/III linker region and protects mice from viremia and viral dissemination following ZIKV or DENV-2 challenge. These data demonstrate that Zika vaccination in a DENV-experienced individual can boost pre-existing flavivirus immunity and elicit protective responses against both ZIKV and DENV. ZPIV vaccination in Puerto Rican individuals with prior flavivirus experience yielded similar cross-neutralizing potency after a single vaccination, highlighting the potential benefit of ZIKV vaccination in flavivirus-endemic areas.

11.
Artículo en Inglés | MEDLINE | ID: mdl-32043531

RESUMEN

BACKGROUND: Zika virus (ZIKV) is a mosquito-borne flavivirus. Outbreaks of ZIKV infection have occurred in Africa, Southeast Asia, the Pacific Islands, the Americas and the Caribbean. Although most ZIKV infections are asymptomatic, cases of neurological manifestations have been described. The aim of the present study was to identify the prevalence of ZIKV infection among the asymptomatic persons in Myanmar in 2018. METHODS: A total of 284 serum samples from apparently healthy persons were collected from Yangon, Myanmar in 2018. They were analysed for ZIKV infection by immunoglobulin M (IgM) capture enzyme-linked immunosorbent assay (ELISA), IgG indirect ELISA, 50% focus reduction neutralization test, real-time reverse transcription polymerase chain reaction (RT-PCR) and conventional RT-PCR. RESULTS: Of the 284 apparently healthy persons, 31.3% were positive for the presence of IgM against ZIKV and 94.3% were positive for anti-flavivirus IgG. Among the ZIKV IgM-positive samples, we confirmed ZIKV infection in 15.8% of asymptomatic persons by neutralization test and real-time RT-PCR. CONCLUSIONS: We conclude that ZIKV infection was increasing among asymptomatic persons in the same area in Myanmar during 2018 compared with 2017. It is highly recommended to strengthen the surveillance system for ZIKV to prevent possible outbreaks.

12.
Emerg Infect Dis ; 26(4)2020 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-32043959

RESUMEN

Zika virus is transitioning to become a long-term public health challenge, and countries should remain informed of the risk for emergence. We developed a stochastic epidemiologic model to profile risk for Zika virus emergence, including trimester-specific fetal risk across time, in all 3,208 counties in the United States, including Puerto Rico. Validation against known transmission in North America demonstrated accuracy to predict epidemic dynamics and absolute case counts across scales (R2 = 0.98). We found that, although sporadic single transmission events could occur in most US counties, outbreaks will likely be restricted to the Gulf Coast region and to late spring through autumn. Seasonal fluctuations in birth rates will confer natural population-level protection against early-trimester infections. Overall, outbreak control will be more effective and efficient than prevention, and vaccination will be most effective at >70% coverage. Our county-level risk profiles should serve as a critical resource for resource allocation.

13.
PLoS Negl Trop Dis ; 14(2): e0008027, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32049958

RESUMEN

Zika virus (ZIKV) has spread in many countries or territories causing severe neurologic complications with potential fatal outcomes. The small primate common marmosets are susceptible to ZIKV, mimicking key features of human infection. Here, a novel simian adenovirus type 23 vector-based vaccine expressing ZIKV pre-membrane-envelope proteins (Sad23L-prM-E) was produced in high infectious titer. Due to determination of immunogenicity in mice, a single-dose of 3×108 PFU Sad23L-prM-E vaccine was intramuscularly inoculated to marmosets. This vaccine raised antibody titers of 104.07 E-specific and 103.13 neutralizing antibody (NAb), as well as robust specific IFN-γ secreting T-cell response (1,219 SFCs/106 cells) to E peptides. The vaccinated marmosets, upon challenge with a high dose of ZIKV (105 PFU) six weeks post prime immunization, reduced viremia by more than 100 folds, and the low level of detectable viral RNA (<103 copies/ml) in blood, saliva, urine and feces was promptly eliminated when the secondary NAb (titer >103.66) and T-cell response (>726 SFCs/106 PBMCs) were acquired 1-2 weeks post exposure to ZIKV, while non-vaccinated control marmosets developed long-term high titer of ZIKV (105.73 copies/ml) (P<0.05). No significant pathological lesions were observed in marmoset tissues. Sad23L-prM-E vaccine was detectable in spleen, liver and PBMCs at least 4 months post challenge. In conclusion, a prime immunization with Sad23L-prM-E vaccine was able to protect marmosets against ZIKV infection when exposed to a high dose of ZIKV. This Sad23L-prM-E vaccine is a promising vaccine candidate for prevention of ZIKV infection in humans.

14.
J Virol ; 2020 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-32051274

RESUMEN

Zika virus (ZIKV) is a major human pathogen. ZIKV can replicate in female and male reproductive organs, thus facilitating the human-human transmission cycle. Viral shedding in the semen can increase the risk of ZIKV transmission through sexual mode. Therefore, the vaginal and anorectal mucosa are relevant sites for ZIKV infection. However, the pathobiology of ZIKV transmission through rectal route is not well understood. Here, we utilize a mouse model system to investigate the immuno-pathological consequences following ZIKV infection of the rectal mucosa compared to a subcutaneous route of infection. We show that ZIKV-rectal inoculation results in viremia with subclinical infection. ZIKV infects the mucosal epithelium and submucosal dendritic cells, inducing immune and inflammatory cell infiltration. Rectal transmission of ZIKV resulted in the generation of serum neutralizing antibody responses. Mass cytometry analyses of splenocytes showed a significantly reduced level of inflammatory monocyte and neutrophil cellular responses in the rectal route group. Furthermore, immunological priming through the rectal mucosa with an attenuated ZIKV strain resulted in significant protection from lethal subcutaneous ZIKV challenge, further eliciting robust memory CD4+ and CD8+ T-cell and ZIKV-specific serum neutralizing antibody responses. Thus, our study provides deeper immuno-pathobiological insights on rectal transmission and highlights a rational strategy for mucosal immunization. This model system recapitulates clinical aspects of human ZIKV disease outcome, where most infections are well controlled and result in subclinical and asymptomatic outcomes.IMPORTANCE. Zika virus is a clinically significant human pathogen that is primarily transmitted and spread by Aedes species mosquitoes, but that is also sexually transmissible. The recent pandemic in the America's led to an unprecedented increase of newborn babies with developmental brain and eye abnormalities. To date, there is no licensed vaccine or therapeutic intervention available for the fight against ZIKV. Understanding the sexual transmission of ZIKV through vaginal and rectal routes is necessary to restrict virus transmission and spread. This study examines the early immunological and pathological consequences of rectal and subcutaneous routes of ZIKV infection using a mouse model. We characterized the primary target cells of ZIKV infection and the subsequent mucosal immune responses to infection, and demonstrate the protective effect of mucosal rectal immunization using an attenuated ZIKV strain. This mucosal vaccination approach can be further developed to prevent future ZIKV outbreaks.

15.
Expert Rev Vaccines ; 2020 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-32077343

RESUMEN

INTRODUCTION: Aedes-borne arboviruses imposes significant economic and public health costs inAreas covered: We performed a systematic review of the economic evidence surrounding aedes-borne arboviruses and strategies to prevent and control these diseases to inform disease control policy decisions and research directions. We searched four databases covering an 18-year period (2000-2018) to identify arboviral disease-related cost of illness studies, cost studies of vector control and prevention strategies, cost-effectiveness analyses and cost-benefit analyses. We identified 74 published studies that revealed substantial global total costs in yellow fever virus and dengue virus ranging from $2.1 billion - 57.3 billion. Cost studies of vector control and surveillance programs are limited, but a few studies found that costs of vector control programs ranged from $5.62to $73.5 million. Cost-effectiveness evidence was limited across Aedes-borne diseases, but generally found targeted dengue vaccination programs cost-effective. This review revealed insufficient economic evidence for vaccine introduction and implementation of surveillance and vector control programs.Expert opinion: Evidence of the economic burden of aedes-borne arboviruses and the economic impact of strategies for arboviral disease prevention and control is critical to inform policy decisions and to secure continued financial support for these preventive and control measures.

16.
Artículo en Inglés | MEDLINE | ID: mdl-32078028

RESUMEN

Recently, Zika virus (ZIKV) has become more widespread, thus attracting global attention. The vaccine against Japanese encephalitis virus (JEV) is currently used in China, being included in planned immunisation regimes. Although ZIKV and JEV are closely related mosquito-borne Flaviviruses, and a complex cross-immune response within flaviviruses has been demonstrated, the effect of JEV vaccination on ZIKV infection has not been well described. Thus, this study aimed to explore the impact of different titres of anti-JEV antibodies (Abs) against ZIKV infection using sera from healthy human donors in Guangzhou and anti-JEV rabbit polyclonal antibodies (pAbs) in vitro and vivo. Human anti-JEV Ab titres were tested at decreasing concentrations as the age increased. A neutralising effect on ZIKV infection was observed when anti-JEV Ab titres in human sera or rabbit pAbs were high (the corresponding age was under 30 years). Even though a lower titre in human sera showed no apparent effect, whereas rabbit pAbs had an antibody-dependent enhancement(ADE)effect, we proved an ADE effect in vivo for the first time. This study suggests that individuals over 60 years of age are at high risk for JEV and ZIKV infection, and screening this age group for infection should strengthen. Furthermore, a deep exploration of the relationship between anti-JEV Abs and ZIKV infection is needed.

18.
Virology ; 543: 34-42, 2020 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-32056845

RESUMEN

Zika Virus (ZIKV) is a Flavivirus transmitted primarily via the bite of infected Aedes aegypti mosquitoes. Globally, 87 countries and territories have recorded autochthonous mosquito-borne transmission of ZIKV as at July 2019 and distributed across four of the six WHO Regions. Outbreaks of ZIKV infection peaked in 2016 and declined substantially throughout 2017 and 2018 in the Americas region. There is the likely risk for ZIKV to spread to more countries. There is also the potential for the re-emergence of ZIKV in all places with prior reports of the virus transmission. The current status of ZIKV transmission and spread is, however, a global health threat, and from the aforementioned, has the potential to re-emerge as an epidemic. This review summarizes the past and present spread of ZIKV outbreak-2007-2019, the genome, transmission cycle, clinical manifestations, vaccine and antiviral drug advancement.

19.
Sci Adv ; 6(5): eaaw7449, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32064329

RESUMEN

Disease epidemics and outbreaks often generate conspiracy theories and misperceptions that mislead people about the risks they face and how best to protect themselves. We investigate the effectiveness of interventions aimed at combating false and unsupported information about the Zika epidemic and subsequent yellow fever outbreak in Brazil. Results from a nationally representative survey show that conspiracy theories and other misperceptions about Zika are widely believed. Moreover, results from three preregistered survey experiments suggest that efforts to counter misperceptions about diseases during epidemics and outbreaks may not always be effective. We find that corrective information not only fails to reduce targeted Zika misperceptions but also reduces the accuracy of other beliefs about the disease. In addition, although corrective information about the better-known threat from yellow fever was more effective, none of these corrections affected support for vector control policies or intentions to engage in preventive behavior.

20.
Antiviral Res ; : 104749, 2020 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-32081740

RESUMEN

Flaviviruses constitute a public health concern because of their global burden and the lack of specific antiviral treatment. Here we investigated the antiviral activity of the alkaloid anisomycin against dengue (DENV) and Zika (ZIKV) viruses. At non-cytotoxic concentrations, anisomycin strongly inhibited the replication of reference strains and clinical isolates of all DENV serotypes and Asian and African strains of ZIKV in Vero cells. Anisomycin also prevented DENV and ZIKV multiplication in human cell lines. While initial steps of DENV and ZIKV replicative cycle were unaffected, a high inhibition of viral protein expression was demonstrated after treatment with anisomycin. DENV RNA synthesis was strongly reduced in anisomycin treated cultures, but the compound did not exert a direct inhibitory effect on 2' O-methyltransferase or RNA polymerase activities of DENV NS5 protein. Furthermore, anisomycin-mediated activation of p38 signaling was not related to the antiviral action of the compound. The evaluation of anisomycin efficacy in a mouse model of ZIKV morbidity and mortality revealed that animals treated with a low dose of anisomycin exhibited a significant reduction in viremia levels and died significantly later than the control group. This protective effect was lost at higher doses, though. In conclusion, anisomycin is a potent and selective in vitro inhibitor of DENV and ZIKV that impairs a post-entry step of viral replication; and a low-dose anisomycin treatment may provide some minimal benefit in a mouse model.

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